Immunostains after glutaraldehyde-based tissue fixation.
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Antigens↗
Biomedical subjects
R J Cohen
Publications and source records attributed to R J Cohen.
Annual report of the Section on Public Health and Preventive Medicine.
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Annual Reports as Topic↗
Distinction between intraductal carcinoma of the prostate (IDC-P), high-grade dysplasia (PIN), and invasive prostatic adenocarcinoma, using molecular markers of cancer progression.
BACKGROUND: Prostate ducts and acini whose lumens are filled with malignant cells represent a well-recognized histological pattern recently termed intraductal carcinoma of the prostate (IDC-P). These tumors are often associated with rapid disease progression, and most recur after radical surgery. Controversy exists as to whether IDC-P should be recognized as a separate entity, an extension of high-grade dysplasia (PIN) or invasive carcinoma as described by the Gleason grading system. This study investigates the use of molecular markers in defining the position of IDC-P in the evolutionary hierarchy of prostate cancer progression. METHODS: IDC-P, high-grade dysplasia, and invasive cancers from a cohort of 20 selected radical prostatectomy specimens were screened for loss of heterozygosity (LOH), using 12 polymorphic microsatellite markers frequently lost in prostate cancer. RESULTS: LOH was absent in Gleason grade 3 cancer, infrequent in high-grade dysplasia (9%) and Gleason grade 4 cancer (29%), but common in IDC-P (60%). In IDC-P, and to a lesser extent Gleason grade 4 cancers, multiple sites of allelic loss in individual cases were usual. CONCLUSIONS: Allelic instability provides further evidence that IDC-P is not a simple extension of dysplasia, nor does it represent invasion of Gleason grade 3 cancers into the ductal/acinar system. IDC-P and Gleason grade 4 cancer represent late but possibly separate events in prostate cancer evolution.
Adenocarcinoma↗
Predictive value of T-wave alternans for arrhythmic events in patients with congestive heart failure.
Measurement of microvolt level T-wave alternans in the surface electrocardiogram is a novel way to assess the risk of ventricular arrhythmias. Seven tests of arrhythmic risk, including T-wave alternans, were undertaken in 107 consecutive patients with congestive heart failure and no history of sustained ventricular arrhythmias; the patients were followed up for arrhythmic events during the next 18 months. Of the patients with events, 11 had positive and two indeterminate T-wave alternans results; there were no arrhythmic events among patients with negative T-wave alternans results. Of the seven tests, only T-wave alternans was a significant (p=0.0036) and independent predictor of arrhythmic events.
Arrhythmias, Cardiac↗
Identification of the glycosaminoglycan keratan sulfate in the prostatic secretory cell.
BACKGROUND: Prostate secretory granules (PSG) represent the basic secretory unit of the prostate gland, containing many of its exocrine proteases. Recent analysis of intraluminal corpora amylacea, a proposed by-product of PSG secretion, detected sulfated glycosaminoglycans (GAG) possibly keratan sulfate (KS), indicating a secretory mechanism for GAG in the human prostate surface epithelial cell. METHODS: Immunostains using anti-KS and anti-prostate-specific antigen (PSA) were evaluated on 10 sequential radical prostatectomy specimens, three of which had received neoadjuvant antiandrogen therapy. Extracts of normal secretory tissue as well as a sample composed almost entirely of prostatic stroma were subjected to Western blot analysis, using the same antibody panel. RESULTS: Keratan sulfate secretion from the normal prostate epithelial cell has been confirmed and correlates, as does PSA, with the presence of cytoplasmic PSG. No such correlation exists in most adenocarcinomas or in benign epithelium after androgen ablation. Western blot analyses confirmed tissue immunostains and demonstrated a secretory proteoglycan of 70-95 kDa. CONCLUSIONS: Recognition of PSG heralds a novel secretory mechanism within the human prostate gland that is linked to the secretion of KS. The role of KS in normal prostate secretion remains unknown, although it appears downregulated in neoplastic and androgen-ablated cells.
Aged↗
Images in cardiovascular medicine. T-wave alternans preceding torsade de pointes ventricular tachycardia.
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Aged↗
Patterns of differentiation and proliferation in intraductal carcinoma of the prostate: significance for cancer progression.
BACKGROUND: Cribriform prostatic intraepithelial neoplasia (C-PIN) identifies a unique histological pattern: dysplastic cells line ductal/acinar walls but also span across gland lumens. C-PIN is distinct from other forms of dysplasia; it is seldom seen except within invasive cancer, it is more frequent in larger/higher-grade cancers; and it appears to contribute independently to aggressive behavior. Hence, C-PIN may represent a separate, more aggressive entity: intraductal carcinoma of the prostate (IDC-P). Here, support for that distinction stems from a histologic/biologic subclassification of IDC-P, whose elements are linked to features of invasive cancer. METHODS: Histologic criteria were tested against 26 radical prostatectomies, using immunostains for prostate-specific antigen, MUC-2, androgen receptor (differentiation), and Ki-67 (proliferation). Invasive cancer grade, stage, and follow-up were compared. RESULTS: Architecture of the central (luminal) cell compartment defined three subclasses of IDC-P: A (trabecular), B (cribriform), and C (solid/comedo), which represented progressive dedifferentiation with a reciprocal increase in proliferation. The IDC-P subpattern correlated with cancer stage, grade, and clinical course. CONCLUSIONS: IDC-P is a separate entity, distinct from PIN; cancers associated with IDC-P are more aggressive than those associated with only PIN. It comprises a spectrum of histological patterns which appear to be determined in concert with invasive cancer, whose prognosis it worsens.
Carcinoma↗
Luminal contents of benign and malignant prostatic glands: correspondence to altered secretory mechanisms.
Recent changes in tissue fixation strategy, using glutaraldehyde, have clarified the secretory mechanisms of the normal prostate identifying cytoplasmic prostatic secretory granules, structures not preserved by formalin fixation. This normal secretory mechanism was absent in most adenocarcinomas, depicting an important metabolic change in transformed prostate cells. The current study further investigates differences between benign and malignant prostate secretion and relates them to the production of corpora amylacea by benign glands and crystalloids or mucin by cancer. In all normal prostate cells examined (6 cases), prostate secretory granules (PSG) were approximately 1-microm, brightly eosinophilic granules filling the cytoplasm of secretory cells and released in packets by a specialized apocrine cell structure. After apocrine decapitation and luminal dispersal, some of the cytoplasmic and PSG remnants condensed to form eosinophilic bodies (EB) with a glycoprotein rim and central protein core. EB were observed adsorbing and layering onto the surface of prostatic corpora amylacea representing their chief mode of enlargement. Biochemical analysis and x-ray diffraction studies confirmed sulfated glycosaminoglycans of similar structure as the main constituent of both PSG and corpora amylacea. Peripheral zone amphiphilic "dark cell" carcinoma (9 cases) contained almost no PSG, and showed neither apical decapitation nor EB formation, but mucin secretion was frequently detected. Crystalloids that share the same staining characteristics and sulfur content as PSG and corpora amylacea were identified in 3 selected "clear cell" carcinomas, all of which showed at least focal PSG secretion. The recognition of these differing secretory mechanisms and their deviation from normal further defines the histological criteria and spectrum of prostate malignancy.
Acid Phosphatase↗
Prostate secretory granules in normal and neoplastic prostate glands: a diagnostic aid to needle biopsy.
The recent increased efficacy of diagnosing prostate carcinoma from needle biopsy can be attributed to the accelerated biopsy rate as a result of cancer screening, the greater number of core samples per set, and the increased ability to identify malignancy in progressively smaller gland foci. This improvement in histological judgement has been facilitated by more sophisticated histological criteria, which in turn depend largely on an increasing knowledge of normal histological features and their abnormal counterparts. The recent discovery of the prostate secretory granule (PSG) as part of the normal secretory mechanism has prompted our study of the PSG as a possible additional criterion for distinction between benign and malignant cells in biopsy samples. The proper delineation of PSG required glutaraldehyde-based fixation, but this change in fixation showed additional diagnostic advantages. We quantitated PSG depletion in 150 sequential core biopsy samples, evaluating benign epithelium, dysplasia (PIN), Gleason grade 3, and grade 4 carcinoma separately. Overall, 80% of carcinomas and 63% of high-grade dysplasias were markedly depleted of PSG such that no granules were seen at low-power magnification with routine haematoxylin and eosin stains. This contrast between benign and malignant epithelium was especially prominent in small carcinoma foci greatly assisting in cancer recognition. Comparison between all groups showed an advantage of glutaraldehyde-based tissue fixation over formalin fixation for prostate needle biopsy specimens, providing clear resolution of cytological detail a well as an additional histologic criterion for cancer diagnosis. HUM PATHOL 31:1515-1519.
Adenocarcinoma↗
Exclusively breastfed, low birthweight term infants do not need supplemental water.
UNLABELLED: Breast milk intake, urine volume and urine-specific gravity (USG) of exclusively breastfed, low birthweight (LBW) term male infants in Honduras were measured during 8-h periods at 2 (n = 59) and 8 (n = 68) wk of age. Ambient temperature was 22-36 degrees C and relative humidity was 37-86%. Maximum USG ranged from 1.001 to 1.012, all within normal limits. CONCLUSIONS: We conclude that supplemental water is not required for exclusively breastfed, LBW term infants, even in hot conditions.
Breast Feeding↗
Variant chromophobe renal cell carcinoma.
Separation of renal cell tumors into different prognostic groups is an imperative function of the diagnostic pathologist. Recently, chromophobe renal carcinoma has been described as a tumor that is morphologically distinct from conventional "clear cell" carcinoma and that has a low metastatic potential. Identification is based on routine light microscopic features and is confirmed by special stains, immunohistochemistry, and electron microscopy. We present a variant of chromophobe renal carcinoma that did not show the typical cytomorphologic features on light microscopy after formaldehyde fixation. After fixation in Solufix (a commercial fixative), these features were recognized and the diagnosis was confirmed. The tumor also showed an unusual form of calcification and psammoma body formation not previously recognized in chromophobe tumors. Molecular biological assessment was inconclusive, but excluded a chromosome 3p deletion usually found in conventional renal carcinoma. The use of a different primary fixative may provide a cost-effective screening tool to detect variant renal tumors and may have important prognostic implications.
Aged↗
Sarcomatoid renal cell carcinoma of papillary origin. A case report and cytogenic evaluation.
Sarcomatoid renal cell carcinoma (SRCC) is an aggressive tumor variant thought to arise predominantly from dedifferentiation of clear cell carcinoma. A few reports of SRCC associated with non-clear cell tumors led to the presumption that SRCC may arise from any renal cell carcinoma, although direct evidence of this is lacking. Cytogenetic studies on 3 previously documented SRCCs associated with papillary renal cancers showed either 3p deletions or absence of trisomy 7, 17 in the sarcomatoid tumors, suggesting origin from a coexistent clear cell tumor. The present case represents the first conclusive evidence of direct progression of non-clear cell carcinoma to SRCC with both tumor components containing multiple copies of chromosomes 7 and 17. Many genetic anomalies, including p53 mutations, frequently recognized in SRCC were not recognized in this case, highlighting the importance of cytogenetic evaluation of all SRCC. The patient is well and without evidence of tumor progression 1 year after surgery, and the sinister outlook of SRCC in association with clear cell carcinoma may not apply in SRCC of non-clear cell origin.
Aged↗
A conscious sheep model for the examination of arterial and cardiopulmonary baroreceptors in the dynamic closed-loop control of Total Peripheral Resistance.
In this study we designed and employed a novel experimental animal model for the examination of arterial and cardiopulmonary baroreceptors in the dynamic closed-loop short-term cardiovascular control of total peripheral resistance, and applied system identification to the analysis of fluctuations in mean arterial pressure, right atrial transmural pressure, and Total Peripheral Resistance to characterize quantitatively the physiologic mechanisms responsible for the couplings between these variables. For this purpose, conscious sheep were used; where both types of baroreceptors were exposed simultaneously to random independent beat pressure variations over a small range around their operating points (via atrial pacing and occlusion of the inferior vena cava), while total peripheral resistance was measured. Subsequently, system identification was applied to the analysis of beat-to-beat fluctuations in the measured signals.
Animals↗
A noninvasive method for total peripheral resistance baroreflex identification.
We developed a noninvasive method for estimating the static gains of the arterial and cardiopulmonary total peripheral resistance (TPR) baroreflexes. The method involves a system identification analysis of beat-to-beat fluctuations in arterial blood pressure (ABP), cardiac output (CO), and stroke volume (SV) in order to identify two transfer functions relating CO fluctuations to ABP fluctuations and SV fluctuations to ABP fluctuations. The static gains of each of the TPR baroreflexes may then be computed from the static gains of the two identified transfer functions. In order to evaluate the method, we constructed a computer model of the human cardiovascular system. We applied the method to data generated from the computer model and found close agreement between the estimated and actual static gains of the model TPR baroreflexes. We also applied the method to experimental human data and obtained encouraging results. These results motivate the experimental validation of the method.
Baroreflex↗
Accuracy of a single equivalent moving dipole model in a realistic anatomic geometry torso model.
In this study, we investigated the accuracy of an algorithm to identify the spatial single equivalent moving dipole parameters in a realistic anatomic geometry torso model from potentials at the body surface. Specifically we investigated the effect of measurement noise, and dipole position and orientation in the accuracy of the algorithm. The boundary element method was used to calculate the forward potential distribution at 64 electrode positions on the body surface due to a point dipole. The mean and standard deviation of the distance of the true (obtained in the forward potential calculation) minus the estimated dipole location (obtained from the inverse algorithm) was estimated for each of the above three cases. Our results indicate that the dipole position has the most significant influence on the accuracy of our inverse algorithm.
Algorithms↗
Comparative study of distraction versus topical anesthesia for pediatric pain management during immunizations.
This study compared distraction, an anesthetic (eutectic mixture of local anesthetics [EMLA]), and typical care during pediatric immunizations. Participants were 39 4th graders receiving a 3-injection vaccination series over a 6-month period. Children displayed low distress despite reporting moderate anxiety and pain. Distraction resulted in more nurse coaching and child coping and less child distress than did EMLA or typical care on an observational measure. EMLA did not result in increased child coping or decreased distress. In fact, the nurse coached more, and trends suggested that children coped more with typical care than with EMLA. Whereas participant ratings and heart rate did not differ among conditions, all 3 conditions demonstrated improvements over time with these measures. Satisfaction ratings suggested that children preferred the treatments to typical care, whereas the nurse appreciated aspects of each of the conditions. Finally, distraction was more economical than EMLA.
Anesthetics, Local↗
A population-based study of clinical and pathological prognostic characteristics of men with familial and sporadic prostate cancer.
OBJECTIVES: To compare traditional prognostic characteristics of familial vs sporadic prostate cancers and to investigate potential detection biases arising from differences in the use of screening and investigative procedures. PATIENTS AND METHODS: Familial and sporadic cancers were identified in a population-based sample of incident prostate cancers (total 318) in Auckland, New Zealand. To examine the potential for detection biases in these comparisons, the sociodemographic and clinical characteristics were determined according to family history status for a sample of 959 patients newly referred to Auckland urology clinics by general practitioners for the investigation of prostate-related conditions. RESULTS: Compared with sporadic prostate cancers, familial cancers were more likely to be diagnosed in patients at a younger age (P=0.05), after asymptomatic serum prostate-specific antigen (PSA) screening (P=0. 02), and to include a lower proportion with extraprostatic disease (P=0.009) and serum PSA levels before diagnosis of >20 ng/mL (P=0. 04). This was consistent with the observed trend for patients referred to urology clinics with a positive family history to be of higher socio-economic and educational status and to more frequently undergo screening and biopsy investigation. CONCLUSION: Familial prostate cancers appeared to be diagnosed at an earlier stage of disease progression in this study population, possibly as the result of the higher socio-economic status and greater use of screening and investigative procedures amongst patients reporting a positive family history. These features reduce the validity of cross-sectional comparisons of prognostic variables for familial vs sporadic prostate cancer and emphasize the need for further longitudinal prognostic studies.
Adult↗
Lymphoepithelioma-like carcinoma of the renal pelvis.
We report the first documented case of undifferentiated carcinoma of the renal pelvis with a prominent lymphoid stroma (lymphoepithelioma-like carcinoma [LELC]). LELCs are morphologically identical to nasopharyngeal carcinoma and are rarely seen in the urinary tract, with only isolated cases involving the urinary bladder and ureter. The tumor was composed entirely of large pale staining malignant epithelial cells with ill-defined borders arranged in syncytial sheets separated by mainly reactive lymphocytes, occasional plasma cells and histiocytes. Tumor cells were immunoreactive to cytokeratin and were negative for leukocyte common antigen. Awareness of LELC is important, as it should be distinguished from lymphoma or inflammatory lesions including, xanthogranulomatous pyelonephritis.
Aged↗